JPH02286619A - Diuretics - Google Patents
DiureticsInfo
- Publication number
- JPH02286619A JPH02286619A JP10758089A JP10758089A JPH02286619A JP H02286619 A JPH02286619 A JP H02286619A JP 10758089 A JP10758089 A JP 10758089A JP 10758089 A JP10758089 A JP 10758089A JP H02286619 A JPH02286619 A JP H02286619A
- Authority
- JP
- Japan
- Prior art keywords
- ursodeoxycholic acid
- glucuronide
- acid
- bile
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002934 diuretic Substances 0.000 title abstract 4
- 229940030606 diuretics Drugs 0.000 title 1
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- 239000000731 choleretic agent Substances 0.000 claims description 7
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 abstract description 16
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 abstract description 16
- 229960001661 ursodiol Drugs 0.000 abstract description 16
- 210000000941 bile Anatomy 0.000 abstract description 14
- 239000003613 bile acid Substances 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 230000029142 excretion Effects 0.000 abstract description 5
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 abstract description 4
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 abstract description 3
- 208000012654 Primary biliary cholangitis Diseases 0.000 abstract description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 abstract description 2
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 229940097043 glucuronic acid Drugs 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract description 2
- 230000001882 diuretic effect Effects 0.000 abstract 3
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000010253 intravenous injection Methods 0.000 abstract 1
- 230000014759 maintenance of location Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 206010008635 Cholestasis Diseases 0.000 description 6
- 230000007870 cholestasis Effects 0.000 description 6
- 231100000359 cholestasis Toxicity 0.000 description 6
- 229930182480 glucuronide Natural products 0.000 description 6
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 150000008134 glucuronides Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 230000001989 choleretic effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229960003080 taurine Drugs 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- BHTRKEVKTKCXOH-UHFFFAOYSA-N Taurochenodesoxycholsaeure Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)CC2 BHTRKEVKTKCXOH-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 208000003167 cholangitis Diseases 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- BHTRKEVKTKCXOH-LBSADWJPSA-N tauroursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-LBSADWJPSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 206010061695 Biliary tract infection Diseases 0.000 description 1
- 208000007238 Postcholecystectomy Syndrome Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NJUISRMVIKYYCN-UHFFFAOYSA-N acetic acid;chloroform;methanol;hydrate Chemical compound O.OC.CC(O)=O.ClC(Cl)Cl NJUISRMVIKYYCN-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 208000003770 biliary dyskinesia Diseases 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- 230000008560 physiological behavior Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明はウルソデオキシコール酸−３−グルクロニドを
有効成分とする利胆剤に関する。ウルソデオキシコール
酸−３−グルクロニドは、ウルソデオキシコール酸の３
位とグルクロン酸の１位とが縮合した化合物であり、以
下の構造式を有する。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a choleretic agent containing ursodeoxycholic acid-3-glucuronide as an active ingredient. Ursodeoxycholic acid-3-glucuronide is the 3-glucuronide of ursodeoxycholic acid.
It is a compound in which the position and the 1st position of glucuronic acid are condensed, and has the following structural formula.
従来の技術
利胆剤は、肝臓からの胆汁排泄を増加させ、胆汁うつ滞
を改善する作用を持ち、非発作時の胆石症、胆道ジスキ
ネジー、胆嚢・胆管炎の炎症消退期、胆嚢切除後症候群
、急性胆汁うつ滞及び胆道感染症等にも使用されている
薬剤である。Conventional choleretic agents have the effect of increasing bile excretion from the liver and improving cholestasis, and are effective against non-attack cholelithiasis, biliary dyskinesia, inflammatory resolution phase of gallbladder/cholangitis, and post-cholecystectomy syndrome. This drug is also used for acute cholestasis and biliary tract infections.
ウルソデオキシコール酸−３−グルクロニドは、そのナ
トリウム塩がすでに知られておりしケミカル・ファーマ
シューティカル・ブレティン（Ｃｈｅ−ｍｉｃａｌ ＆
Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ
） ２８巻４号１２５８頁１９８０年］、本発明者らに
よって人血清中に微量に存在することも確認されている
［ザ・ジャーナル・オブ・バイオケミストリー（Ｔｈｅ
Ｊｏｕｒｎａｌ ｏｆ Ｂｉｏｃｈｅｍｉｓｔｒｙ
） ９２巻４号９８５頁１９８２年）。Ursodeoxycholic acid-3-glucuronide, whose sodium salt is already known, has been published in the Chemical & Pharmaceutical Bulletin (Chemical & Pharmaceutical Bulletin).
Pharmaceutical Bulletin
) Vol. 28, No. 4, p. 1258, 1980], and the present inventors have also confirmed that it exists in trace amounts in human serum [The Journal of Biochemistry (The
Journal of Biochemistry
) Vol. 92, No. 4, p. 985, 1982).
一方、ウルソデオキシコール酸は、利胆剤として繁用さ
れている薬物であるが、原発性胆汁性肝硬変にも奏効す
ることも報告されている（特開昭６３−１４１９２９号
公報〉。On the other hand, ursodeoxycholic acid is a drug frequently used as a choleretic agent, but it has also been reported to be effective in primary biliary liver cirrhosis (Japanese Patent Application Laid-Open No. 141929/1983).
発明が解決しようとする課題
しかしながら、上記文献には、ウルソデオキシコール酸
−３−グルクロニドの生理学的挙動及び薬理作用につい
ては解明されておらず、それらの示唆もない。Problems to be Solved by the Invention However, the above-mentioned literature does not elucidate the physiological behavior and pharmacological action of ursodeoxycholic acid-3-glucuronide, and there is no suggestion thereof.
本発明者らは、長年、遊離胆汁酸又はそれらのグルクロ
ン酸抱合体、タウリン抱合体もしくは硫酸抱合体等の肝
胆道疾患における病態生理及び臨床応用を研究してきた
ところ、人血清中に微量に存在するウルソデオキシコー
ル酸−３−グルクロニドが、それの遊離体であるウルソ
デオキシコール酸より肝臓からの胆汁排出促進効果が高
く、強力に胆汁うつ滞を改善することを見い出し本発明
に到達した。The present inventors have been studying the pathophysiology and clinical application of free bile acids and their glucuronide, taurine, or sulfate conjugates in hepatobiliary diseases for many years, and found that they exist in trace amounts in human serum. The present inventors have discovered that ursodeoxycholic acid-3-glucuronide, which is a free form of ursodeoxycholic acid, has a higher effect of promoting bile excretion from the liver and strongly improves cholestasis than its free form, ursodeoxycholic acid.
課題を解決するための手段
本発明は、ウルソデオキシコール酸−３−グルクロニド
を有効成分として含有する利胆剤の提供を目的とする。Means for Solving the Problems The present invention aims to provide a choleretic agent containing ursodeoxycholic acid-3-glucuronide as an active ingredient.
ウルソデオキシコール酸−３−グルクロニドは、胆汁酸
のグルクロン酸抱合体の周知な方法を応用して製造する
ことができる。例えば、３α−ヒドロキシ−７β−ホル
ミルオキシ−５β−フラン酸メチルエステルとメチル
２，３．１−トリ０−アセチル−１−デオキシ−α−ブ
ロモ−Ｄグルコピランウロシドとを、ケーニヒークノル
（ＫＯｅｎｉ（ＩＳ−ＫｎＯｒｌ’ ）反応により縮合
させ、得られる７β−ホルミルオキシ−３α−０−（メ
チル２−．３−．４−一トリー〇−アセチルーβ−Ｄ−
グルコピランウロノシル）−５β−フラン酸メチルエス
テルをついでアルカリで加水分解することにより製造す
ることができる。Ursodeoxycholic acid-3-glucuronide can be produced by applying a well-known method for glucuronide conjugation of bile acids. For example, 3α-hydroxy-7β-formyloxy-5β-furanic acid methyl ester and methyl
7β-formyloxy-3α- obtained by condensing 2,3.1-tri0-acetyl-1-deoxy-α-bromo-D glucopyran uroside with Koeni (IS-KnOrl') reaction. 0-(methyl 2-.3-.4-tri-acetyl-β-D-
It can be produced by subsequently hydrolyzing glucopyranuronosyl-5β-furanic acid methyl ester with an alkali.
作用
ウルソデオキシコール酸−３−グルクロニドの利用試験
及び急性毒性試験の結果を以下に詳述する。Effects The results of the utilization test and acute toxicity test of ursodeoxycholic acid-3-glucuronide are detailed below.
〈利用試験〉
外胆汁痩を造設したウィスター系雄性ラット（−群８匹
；体重２５０３前後〉を用い、ウルソデオキシコール酸
を対照薬としてウルソデオキシコール酸−３−グルクロ
ニドの利胆作用を試験した。ウルソデ′オキシコール酸
−３〜グルクロニドは、予め大腿静脈より３％アルブミ
ン液を２．０ｍ１／時の速度で１時間持続注入した各ラ
ットに、ウルソデオキシコール酸−３−グルクロニドの
投与量がラット体重１００９あたり０，２５μｍ。<Usage test> Using ursodeoxycholic acid as a control drug, the choleretic effect of ursodeoxycholic acid-3-glucuronide was tested using male Wistar rats (8 rats in the − group; body weight around 2503 cm) with an external biliary tract. Ursodeoxycholic acid-3-glucuronide was administered to each rat by continuous infusion of 3% albumin solution through the femoral vein at a rate of 2.0 ml/hour for 1 hour. is 0.25 μm per 1009 rat body weight.
７分になるよう当該アルブミン液に添加して静注した。It was added to the albumin solution for 7 minutes and injected intravenously.
利胆作用は、ウルソデオキシコール酸−３グルクロニド
の投与後１０分毎に４０分間、肝臓から排出される胆汁
を採取し、流量の増加量を測定して評価した。また、採
取した胆汁の一部は、担体がシリカゲル（キーゼルゲル
６０）、展開液がクロロホルム−メタノール−酢酸−水
混合液（容量比６５：２４：１５：９）、発色剤がリン
モリブデン酸、硫酸又はナフトレゾルシンという条件か
らなる薄層クロマトグラフィーに付し、胆汁酸分析を行
った。この胆汁酸分析におけるウルソデオキシコール酸
−３−グルクロニド、ウルソデオキシコール酸及びタウ
ロウルソデオキシコール酸のＲｆ値は、夫々０．３３．
０．９５及び０．３５であった。なお、対照薬のウルソ
デオキシコール酸による利胆作用の試験及び胆汁酸分析
も上記と同様にして行った。結果を第１表に示す。The choleretic effect was evaluated by collecting bile excreted from the liver for 40 minutes every 10 minutes after administration of ursodeoxycholic acid-3 glucuronide and measuring the increase in flow rate. In addition, some of the collected bile was prepared using silica gel (Kieselgel 60) as a carrier, a chloroform-methanol-acetic acid-water mixture (volume ratio 65:24:15:9) as a developing solution, and phosphomolybdic acid and sulfuric acid as coloring agents. Alternatively, bile acids were analyzed by thin layer chromatography using naphresorcin. In this bile acid analysis, the Rf values of ursodeoxycholic acid-3-glucuronide, ursodeoxycholic acid, and tauroursodeoxycholic acid were each 0.33.
They were 0.95 and 0.35. In addition, a test of choleretic effect using a control drug, ursodeoxycholic acid, and bile acid analysis were conducted in the same manner as above. The results are shown in Table 1.
表中、胆汁流量増加量は、投与開始後１０分毎に４０分
間、ウルソデオキシコール酸−３−グルクロニド投与群
又はウルソデオキシコール酸投与群と薬物無投与群との
胆汁流量の差を夫々求め、これを薬物無投与群における
胆汁流量の百分率で表ボした。In the table, the increase in bile flow rate is determined by calculating the difference in bile flow rate between the ursodeoxycholic acid-3-glucuronide administration group or the ursodeoxycholic acid administration group and the drug-free group for 40 minutes every 10 minutes after the start of administration. This was expressed as a percentage of bile flow in the drug-free group.
第１表から明白なように、ウルソデオキシコール酸−３
−グルクロニドは、ウルソデオキシコール酸に比べ、肝
臓からの胆汁排出を約２．３倍にまで促進し、胆汁うつ
滞を顕著に改善していることが認められる。As is clear from Table 1, ursodeoxycholic acid-3
- Glucuronide has been found to promote bile excretion from the liver approximately 2.3 times as much as ursodeoxycholic acid, and to significantly improve cholestasis.
また、薄層クロマトグラフィーによる胆汁酸分析によれ
ば、ウルソデオキシコール酸投与群では、投与したウル
ソデオキシコール酸のほとんどか肝臓でタウリン抱合さ
れ、胆汁中にタウロウルソデオキシコール酸として排出
されたのに対し、ウルソデオキシコール酸−３−グルク
ロニド投与群では、ウルソデオキシコール酸−３−グル
クロニドの大部分か胆汁中に未変化体のまま排出された
のが夫々確認された。この事実と上記第１表の試験結果
を合わせて考慮すると、ウルツデオキシコル酸−３−グ
ルクロニドは、肝臓でのタウリン抱合を受けることなく
、ウルソデオキシコール酸に比べ極めて効率的に胆汁流
量を増加させ、胆汁うつ滞に奏効することが考察される
。Furthermore, according to bile acid analysis using thin-layer chromatography, in the ursodeoxycholic acid-administered group, most of the administered ursodeoxycholic acid was conjugated with taurine in the liver and excreted into bile as tauroursodeoxycholic acid. On the other hand, in the ursodeoxycholic acid-3-glucuronide administration group, it was confirmed that most of the ursodeoxycholic acid-3-glucuronide was excreted unchanged into bile. Considering this fact together with the test results in Table 1 above, urtudeoxycholic acid-3-glucuronide increases bile flow much more efficiently than ursodeoxycholic acid without undergoing taurine conjugation in the liver. It is considered to be effective for cholestasis.
〈急性毒性試験〉
５週令のＩＣＲ系雄性マウス及びウィスター系雄性ラッ
トを用い、ウルソデオキシコール酸−３グルクロニドの
急性毒性（ＬＤ５０）を試験した。<Acute toxicity test> The acute toxicity (LD50) of ursodeoxycholic acid-3 glucuronide was tested using 5-week-old ICR male mice and Wistar male rats.
ＬＤ５ｏ値は、マウスでは経口で５’ｊ／Ｋｇ以上、静
脈内で４００ｍ’ｊ／に’ｊ以上でめった。また、ラッ
トでは経口で４９／に３以上、静脈内で３５０ｍ９／Ｋ
ｇ以上であった。従って、ウルソデオキシコール酸３−
グルクロニドは毒性の低い薬物と言うことかできる。In mice, the LD5o value was 5'j/Kg or more for oral administration and 400 m'j/'j or more for intravenous administration. In addition, in rats, oral doses of 49/K or more, intravenous doses of 350 m9/K or more.
It was more than g. Therefore, ursodeoxycholic acid 3-
Glucuronide can be said to be a drug with low toxicity.
〈用法・用量〉
ウルソデオキシコール酸−３−グルクロニドの用量は、
患者の年齢、症状又は併用薬等が考慮される。成人の一
日用量は、経口で１０〜４０００ｍｇ、好ましくは、１
００〜２０００ｍｙ、静注で５〜１０１００Ｏ、好まし
くは、５０〜６００ｍｙとし、これを１〜６回、好まし
くは、１〜３回に分けて用いるのが一般に望ましい。<Dosage and Administration> The dose of ursodeoxycholic acid-3-glucuronide is
The patient's age, symptoms, or concomitant medications are taken into consideration. The daily dose for adults is 10-4000 mg orally, preferably 1
It is generally desirable to divide the dose into 1 to 6 times, preferably 1 to 3 times.
本発明の利胆剤には、有効成分のウルソデオキシコール
酸−３−グルクロニドに生理的に無害な固体もしくは液
体の製剤担体を配合した錠剤、カプセル剤、散剤、細粒
剤、顆粒剤、水剤、シロップ剤、懸濁剤、乳剤又は注射
剤等の薬剤組成物も包含する。製剤担体としては、市販
のウルソデオキシコール酸製剤に通常用いられるものは
か、種々の賦形剤、結合剤、崩壊剤、潤沢剤、被覆剤、
溶解補助剤、乳化剤、懸濁化剤、安定化剤又は溶剤等も
使用することができる。The choleretic agents of the present invention include tablets, capsules, powders, fine granules, granules, and water-based preparations containing the active ingredient ursodeoxycholic acid-3-glucuronide and a physiologically harmless solid or liquid carrier. It also includes pharmaceutical compositions such as tablets, syrups, suspensions, emulsions or injections. Pharmaceutical carriers include those commonly used in commercially available ursodeoxycholic acid formulations, as well as various excipients, binders, disintegrants, lubricants, coating agents,
Solubilizers, emulsifiers, suspending agents, stabilizers or solvents can also be used.
発明の効果
ウルソデオキシコール酸−３−グルクロニドは、「ウル
ソデオキシコール酸より効率的に肝臓からの胆汁排出を
促進し、顕著に胆汁うつ滞を改善せしめることから、本
化合物を有効成分として含有する薬剤は、強力な利胆剤
として利用することができる。更に、ウルソデオキシコ
ール酸と同様に、原発性胆汁性肝硬変への適用も期待で
きる。Effects of the Invention Ursodeoxycholic acid-3-glucuronide "promotes bile excretion from the liver more efficiently than ursodeoxycholic acid and significantly improves cholestasis, so it contains this compound as an active ingredient." The drug can be used as a powerful choleretic agent.Furthermore, like ursodeoxycholic acid, it can also be expected to be applied to primary biliary cirrhosis.
Claims (1)
効成分として含有することを特徴とする利胆剤。(1) A choleretic agent characterized by containing ursodeoxycholic acid-3-glucuronide as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10758089A JPH0667846B2 (en) | 1989-04-28 | 1989-04-28 | Choleretic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10758089A JPH0667846B2 (en) | 1989-04-28 | 1989-04-28 | Choleretic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02286619A true JPH02286619A (en) | 1990-11-26 |
| JPH0667846B2 JPH0667846B2 (en) | 1994-08-31 |
Family
ID=14462772
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10758089A Expired - Lifetime JPH0667846B2 (en) | 1989-04-28 | 1989-04-28 | Choleretic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0667846B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994022896A1 (en) * | 1993-03-31 | 1994-10-13 | Tokyo Tanabe Company Limited | Cholestasis ameliorant |
| WO2001021642A1 (en) * | 1999-09-22 | 2001-03-29 | Aventis Pharma Deutschland Gmbh | 4-benzylaminoquinoline conjugates with bile acid and their heteroanalogues, methods for producing the same, medicaments containing these compounds and their use |
| JP2003508513A (en) * | 1999-09-02 | 2003-03-04 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Bile acid-substituted phenylalkenoylguanidines, methods for their preparation, their use as medicaments or diagnostics, and medicaments containing them |
-
1989
- 1989-04-28 JP JP10758089A patent/JPH0667846B2/en not_active Expired - Lifetime
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994022896A1 (en) * | 1993-03-31 | 1994-10-13 | Tokyo Tanabe Company Limited | Cholestasis ameliorant |
| JP2003508513A (en) * | 1999-09-02 | 2003-03-04 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Bile acid-substituted phenylalkenoylguanidines, methods for their preparation, their use as medicaments or diagnostics, and medicaments containing them |
| JP4768941B2 (en) * | 1999-09-02 | 2011-09-07 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Bile acid-substituted phenylalkenoylguanidines, processes for their preparation, their use as medicaments or diagnostics, and medicaments containing them |
| WO2001021642A1 (en) * | 1999-09-22 | 2001-03-29 | Aventis Pharma Deutschland Gmbh | 4-benzylaminoquinoline conjugates with bile acid and their heteroanalogues, methods for producing the same, medicaments containing these compounds and their use |
| JP2003510255A (en) * | 1999-09-22 | 2003-03-18 | アベンティス・ファーマ・ドイチユラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 4-Benzylaminoquinoline conjugates with bile acids and their hetero-analogs, their preparation, medicaments containing these compounds and their use |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0667846B2 (en) | 1994-08-31 |
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